In damaged tissues, inflammatory mediators (such as cytokines or proteolytic enzymes) are up-regulated. These mediators are part of the wound healing response, but if up-regulated chronically, these mediators can cause a chronic inflammation that contributes to joint destruction. Osteoarthritis (OA) is the most prevalent disease in developed countries, affecting 27 million people in the U.S. (Lawrence R C, et al. (2008) Arthritis Rheum 58:26-35: Helmick C G, et al. (2008) Arthritis Rheum 58:15-25) and resulting in annual U.S. health care expenditures of $186 billion (Kotlarzz, et al, (2009) Arthritis Rheum 60:3546-3553). There is a critical lack of disease modifying OA drugs (DMOAD), due in part to an inability to clinically detect early stage OA. Though promising biomarkers in urine and serum have been identified through the OA Biomarkers Global Initiative, biochemical changes detectable in the urine or serum are not specific to an affected joint, are dilute relative to levels within the affected joint, and may not be detectable at the earliest stages of OA.
In order to accurately diagnose and assess OA in the earliest stages it is necessary to sample biomarkers in the affected joint, such as the knee. Harvesting biomarkers from the synovial fluid of the knee joint has proven to be challenging. In particular, removal of synovial fluid is difficult because it is an incredibly viscous fluid that usually requires a large needle for its removal. Use of a large needle is difficult in intermediate joints and impossible in smaller joints such as the metacarpalphalanges and facet joints. Removal of synovial fluid from large joints such as the knee or hip, while easier, is still problematic due to a fairly high rate of “dry taps” or inability to remove fluid from those joints.
Accordingly, there is a need for a magnetic micro/nanoparticle-based assay that can harvest biomarkers for diagnosis, prognosis, or treatment of a disease. More specifically, there is a need for a method wherein magnetic micro- and nanoparticles functionalized with molecules that target OA biomarkers are injected into the synovial cavity and harvested using a smaller apparatus and needle.